CN1316247C

CN1316247C - Device and method for acquiring and analyzing physiological liquid

Info

Publication number: CN1316247C
Application number: CNB031309194A
Authority: CN
Inventors: B·索拉布
Original assignee: LifeScan Inc
Current assignee: LifeScan Inc
Priority date: 2002-05-09
Filing date: 2003-05-07
Publication date: 2007-05-16
Anticipated expiration: 2023-05-07
Also published as: IL155342A0; DE60310159T2; HK1057158A1; CA2427843A1; TW200406174A; EP1360934B2; US20030212347A1; EP1360934A1; JP2004000598A; US7343188B2; SG111106A1; US20080009768A1; EP1360934B1; DE60310159D1; DE60310159T3; ATE347306T1; CN1456887A

Abstract

Systems, devices and methods for determining the concentration of physiological fluid analytes are provided. The subject systems have a plurality of biosensor devices present on a disposable cartridge. Each biosensor device includes a biosensor and a skin penetration means. In practicing the subject methods, a movement means of the device is used to move each biosensor device in a first direction that provides for penetration of the skin-piercing means into a skin layer followed by movement of the biosensor in a second direction that provides for removal of the skin-piercing means from the skin layer, where this movement profile provides for physiological fluid access and analyte concentration determination by the analyte sensor means. The subject systems, devices and methods for using the same find use in determining the concentration of a variety of different physiological fluid analytes, and are particularly suited for use in detection of physiological fluid glucose concentration.

Description

Be used to obtain and analyze the device of physiological fluid

Technical field

The field of the invention is an analyte concentration determination, particularly obtains the concentration of physiological fluid and mensuration one or more analytes wherein.

Background technology

Physiological fluid such as blood or the detection of analytes that comes from the product, physiological fluid etc. of blood are more and more important in current society.The detection of analyte chemical examination can be used for multiple application, comprises clinical laboratory inspection and family check etc., and wherein the result of this check plays an important role in the diagnosis of the various patient's condition with in curing.Usually the analyte of being concerned about is included in the glucose that needs analysis in the diabetes treatment, and cholesterol etc.In response to this importance that increases day by day of detection of analytes, developed multiple detection of analytes scheme and the device that can be used for clinic and family's use.

In the analyte concentration of measuring physiologically sample, at first must obtain physiologically sample.Obtain that sample is usually directed to trouble and complicated apparatus, these devices can not easily use, and perhaps cost is too high and can't produce.In addition, the process that obtains sample may be very painful.For example, pain is usually relevant with the size of the pin that is used to obtain physiologically sample and the degree of depth that pin is inserted.According to analyte and the test-types that is adopted, use bigger single needle to wait the sample that extracts aequum usually.

The analyte concentration determination process also relates to multinomial step usually.At first, adopt skin penetrating mechanism such as pin or lancet to obtain sample, this obtaining also relates to use sample collecting mechanism such as kapillary.Then, sample must be sent in verifying attachment such as the calibration tape etc., usually calibration tape be sent in measurement mechanism such as the measuring instrument then.Like this, the step that obtain sample, collected specimens, sample is sent to the analyte concentration in the biology sensor and in the measuring samples is carried out with independent, continuous step and by various devices and instrument usually.

Owing to exist these shortcomings, the patient that need carry out analyte monitoring continually is unwilling oneself is monitored at large.For example concerning the diabetes patient, can't stipulate that the concentration of glucose of measuring them can cause shortage correctly to control the concentration of glucose information necessary by prescription.Concentration of glucose without control is very dangerous, even threatens life.

It is progressive to overcome the shortcoming of above-mentioned detection scheme to have obtained some in the detection of analytes technology.Main progress is the device that will be used for obtaining physiological fluid and be used for the analyte that tracer liquid is concerned about such as the existence of glucose and/or the device of concentration and integrate.More particularly, this integrating device comprises biology sensor, and it has skin-piercing element such as the microneedle that is integrated in wherein.These representative device for example are disclosed in the following U.S. Patent application: No.09/923093; The attorney docket of submitting on the same day with the application is No.LIFE-035, be entitled as the application of " physiologically sample collecting device and using method thereof "; The attorney docket of submitting on the same day with the application is No.LIFE-058, be entitled as the application of " having the molded detection of analytes part that thrusts blade "; And be No.LIFE-073, be entitled as the application of " manufacture method of physiologically sample collecting device " with attorney docket that the application submits on the same day.

Although obtained above-mentioned progress,, people have interest yet splitting the new device and the method for the analyte concentration of hair in measuring physiologically sample always.Wherein interested especially is that exploitation has the analyte concentration determination system and the using method thereof of integrated liquid acquisition and measuring ability, this system and method carries out automatically, so that user's operation is reduced to minimum, and convenient, easily and improved portability.

Summary of the invention

According to the present invention, a kind of system is provided, it comprises multiple arrangement, each described device comprises: (i) at least one skin-piercing element, it is configured to obtain the physiological fluid under the skin surface; (ii) be used to measure the biology sensor of the characteristic of the physiological fluid that is obtained, wherein said skin-piercing element and described biology sensor form one; (iii) physiological fluid transfer path, it extends to described biology sensor from described at least one skin-piercing element, this system also comprises the mechanism that is used to make each described multiple arrangement motion, and the mode of described motion provides by described at least one skin-piercing element and penetrates in the skin surface with the angle that is inclination with respect to skin surface.

The invention provides and be used to obtain physiological fluid and determine wherein system, the apparatus and method of the concentration of one or more analytes.Topic is stated system provides a kind of cassette holder device that includes the biology sensor/skin penetrating/liquid acquisition device of a plurality of special purposes.Cassette holder device of the present invention has the structure on flat or plane, preferably has disc shaped, but also can have elongated shape.Biology sensor/skin penetrating/liquid acquisition device is located in the cassette holder of continuous structure, the path that it preferably equidistantly is spaced from each other and is parallel to the cassette holder motion or rotates.In the dish type cassette holder, this continuous setting is round the circumference of cassette holder.

Topic is stated system and is also comprised shell mechanism, and cassette holder can be packed into wherein.Shell mechanism preferably has towards the part of skin and/or surface, and it can make the part of the cassette holder that installs of packing into wherein and user's skin and put.Shell preferably is configured to and can keeps being attached on the skin in the long term.For this reason, shell can have can be worn on the user limbs zones as " watchband " structure on wrist or the forearm, or have and can form bond contacting structure, for example structure of general plane with suitable position on user's health such as trunk, thigh, buttocks etc.

Each biology sensor/skin penetrating/liquid acquisition device has biology sensor, its be used to thrust, the skin penetrating of incision or skin puncture or thrust part and integrate, also can comprise liquid acquisition passage or transfer path in certain embodiments, it is used for the physiological fluid that sampling in skin obtains is sent to the biology sensor part of device.Biology sensor can have the structure of galvanochemistry, luminosity or the colorimetric that can measure sample liquid.In certain embodiments, biosensor arrangement can have the structure that is substantially the plane, and wherein at least one skin-piercing element extends out from biosensor arrangement.In some this class embodiment, skin-piercing element is extended in the plane identical with the biosensor arrangement on plane basically, and in some other embodiment, skin-piercing element is extended along the direction of the planar structure that is substantially transverse to biosensor arrangement.More particularly, in certain embodiments, biosensor arrangement is configured to calibration tape, and wherein skin-piercing element extends out from element of calibration tape or parts such as substrate, electrode or wall.Some other embodiment provides the frame unit with planar structure, and it has to install and be integrated on the same plane surface but be spaced from each other goes into part with the biology sensor cushion block of the function that promotes this specific device or band and aculea.In some other embodiment, be provided with angled structure, it at least one micromanipulation needle construction, and has supported the chamber of biology sensor at remote extension at its near-end.

Topic is stated system and is also comprised measuring instrument, and it is contained in the shell mechanism to analyze by biology sensor/skin penetrating/resulting physiological fluid of liquid acquisition device.Be provided with connector or contact so that biosensor arrangement is operationally linked to each other with measuring instrument, like this, measuring instrument can offer the signal of necessity biosensor arrangement chemically examining measurement, and comprises the device that is used to measure this measured value.

Topic is stated system and is also comprised a kind of device, it is used for opening with respect to shell mechanism and comes operationally to move as advance and oppositely move topic and state cassette holder, thereby can a biology sensor/skin penetrating/liquid acquisition device be exposed to obtaining the position neutralization and stash on user's skin by this opening.Perhaps, at least a portion that has the shell mechanism of opening is movable, to expose and not expose a biology sensor/skin penetrating/liquid acquisition device.The motion of this cassette holder can be passed through connector or contact with the biosensor arrangement that exposes and operationally link to each other with measuring instrument.

Although biosensor arrangement is with the translation of cassette holder device, but in certain embodiments, each biosensor arrangement operationally links to each other with the cassette holder device, thereby it can move with respect to the cassette holder device, therefore thereby can optimize the angle that dermal fibroblasts is thrust skin, can alleviate patient's pain and the damage of skin.This motion comprises deflection and/or the rotation of biosensor arrangement round a certain axle, and described axle becomes radially because of the mobile path of the translation of cassette holder device with biology sensor or vertically extends.Biosensor arrangement is mainly realized passively with respect to the motion of cassette holder, for example by be fixed on the parts in the shell mechanism with respect to cassette holder, its be used for by the opening on the shell and towards the user obtain that the position promotes or each biology sensor/skin penetrating of deflection/liquid acquisition device, thrust with skin-piercing element and obtain the position and from obtain the position, recall subsequently or retraction mechanism.This parts include but not limited to ramp structure and clamp system.

Topic is stated system and also can be comprised controller, for example is the form of microprocessor, with the function of control survey instrument and the motion of cassette holder and biosensor arrangement, and stores associated data.Controller is programmable, makes to customize its chemical examination scheme and select time according to software algorithm.This algorithm can be used for monitoring the analyte concentration in user's body " continuously ", promptly according to preset program, for example automatically measure analyte concentration in user's body during two or more in the preset time section.System also can be the chemical examination that the user carries out " on request ", and it can have precedence over continuous monitoring scheme like this.This analyte concentration measurement is stored by microprocessor or other memory storage, so that user or doctor retrieve immediately or subsequently.Topic is stated system also can comprise the display device that is used to show result of laboratory test and other relevant information.In certain embodiments, this system comprises and is used for communicating by letter with external device (ED) to transmit and to receive about the information of result of laboratory test, chemical examination scheme, user, disposable cassette holder etc. and the device of data.

When the enforcement topic is stated method, adopt such chemical examination scheme, it comprises that the skin by thrust the user with skin-piercing element obtains physiological fluid, the physiological fluid that is obtained is captured in the biology sensor, and measures one or more target analytes in the physiological fluid.Each chemical examination scheme comprises that the first party of thrusting skin along the skin-piercing element that makes the integral biosensor device always promotes or mobile cassette holder or associated opening, along always mobile cassette holder of the second party that skin-piercing element is extracted out from skin or opening, this mode of motion can obtain physiological fluid and be carried out the mensuration of analyte concentration by biology sensor then.The promotion of cassette holder or opening can be undertaken or be undertaken by the motor that controller is controlled by the user artificially.This promotion and skin penetrating can automatically carry out according to the program of pre-programmed or user's wish.

Topic is stated system, device and using method thereof and is used in and provides repeatably liquid acquisition between biology sensor and the target skin part and the interface of sampling, so that measure the chemical characteristic of sample liquid, the concentration of normally multiple different physiological fluid analytes is the concentration of glucose more at large.Topic is stated the continuous coverage that system and device can be used for the analyte be concerned about, and the problem that can not exist implantable analyte sensor to run into.For example, owing to adopted the painless basically analysis measurement device of special purpose, stimulation and pain have therefore been avoided to the user.In addition, the single measurement mechanism that is adopted need not calibration before use.In addition, for glucose, not only can employing topic state that apparatus and method detect the generation of hypoglycemia and hyperglycaemia situation rapidly and accurately and the participation or the intervention that do not need the user, but also can adopt them easily to predict the generation of hypoglycemia and hyperglycaemia situation, therefore the better treatment of the patient's condition relevant with blood sugar metabolism is provided.Therefore, topic is stated and is invented the major contribution of having represented the present technique field.

Can know these and other purposes, features and advantages of the present invention after the details of the method and system of the present invention that those skilled in the art has introduced in detail below having read.

Description of drawings

Figure 1A is the decomposition view that is suitable for an embodiment of electrochemica biological sensor/skin penetrating/liquid acquisition device of using with cassette holder device of the present invention and system.Figure 1B is the skeleton view of the device that assembles shown in Figure 1A.

Fig. 2 A is the decomposition view that is suitable for an embodiment of the colorimetric used with cassette holder device of the present invention and system or photometric biosensor/skin penetrating/liquid acquisition device.Fig. 2 B is the skeleton view of the device that assembles shown in Fig. 2 A.

Fig. 3 has shown another embodiment that is suitable for electrochemica biological sensor/skin penetrating/liquid acquisition device of using with cassette holder device of the present invention and system.

Fig. 4 has shown another embodiment that is suitable for electrochemica biological sensor/skin penetrating/liquid acquisition device of using with cassette holder device of the present invention and system.

Fig. 5 has shown another embodiment that is suitable for biology sensor/skin penetrating/liquid acquisition device of using with cassette holder device of the present invention and system.Fig. 5 B is the zoomed-in view of the skin-piercing element of Fig. 5 A shown device.

Fig. 6 A is the top view of an embodiment with system of the present invention of user-friendly portable construction.Fig. 6 B is the side view of the B-B along the line of system shown in Fig. 6 A.Fig. 6 C is the backplan of the C-C along the line of system shown in Fig. 6 B.Fig. 6 D has shown Fig. 6 A that is in open mode, and the system shown in 6B and the 6C has shown operationally to be in the interior cassette holder device of the present invention of shell that topic is stated system.

Fig. 7 A is the indicative icon of an embodiment of cassette holder device of the present invention.Fig. 7 B is the partial enlarged view of cassette holder device shown in Fig. 7 A, and it operationally closes with the bottom connection of the system shell of an embodiment with biology sensor telecontrol equipment of the present invention.

Fig. 8 A has schematically shown the embodiment of biology sensor telecontrol equipment of system of the present invention and the Fig. 1 on the cassette holder of the present invention, the progressively motion of biology sensor/skin penetrating shown in 2 or 3/liquid acquisition device to 8F.

Fig. 9 A has schematically shown another embodiment of biology sensor telecontrol equipment of system of the present invention and the progressively motion of the biology sensor/skin penetrating shown in Figure 4 on the cassette holder of the present invention/liquid acquisition device to 9G.

Figure 10 A has schematically shown the progressively motion of the cassette holder of the present invention that adopts biology sensor/skin penetrating shown in Figure 4/liquid acquisition device to 10C.

Figure 11 A has represented to inscribe " watchband " embodiment of the system that states.Figure 11 B has represented to use the topic that also can communicate by letter with it to state " watchband " embodiment of system with telechiric device.

Embodiment

Before introducing the present invention, should understand and the invention is not restricted to the specific embodiment introduced, so the present invention certainly changes.Will also be understood that employed term just is used to introduce the purpose of specific embodiment here, and do not play restriction that this is because scope of the present invention is only limited by claims.

When the scope of numerical value is provided, be to be understood that, be included in the present invention in the higher limit of this scope and each the insertion value between the lower limit and any other value of providing in given scope or insertion value, unless explanation is arranged in the context clearly in addition, otherwise these insertion values are to insert with 1/10th amount of lower limit unit.Got rid of in providing scope under the condition of eliminating value of any appointment, these higher limit and the lower limits more among a small circle in can being included in more independently are also contained in the present invention.Comprised in given scope under the situation of one or two limit value that the excluded scope of the limit value that these are included is also contained in the present invention.

Except as otherwise noted, otherwise all used here technology and scientific words and those of ordinary skill in the art the same meaning generally understood.Though can adopt in enforcement of the present invention or check and the method for introducing here and materials similar or equivalent any method and material, what will introduce below is preferable methods and material.

Must be noted that here with claims in the singulative " " and " this " that use comprised that the quilt of plural form refers to object, unless explanation is clearly arranged in the context in addition.Therefore, for example, " calibration tape " comprised many this calibration tapes, and " this device " comprises one or more devices and equivalent known to those skilled in the art, or the like.

Here the publication of being touched upon for no other reason than that the open of them provide early than submissions day of the present invention.All explanations here all can not be interpreted as, owing to there are these existing inventions, the present invention can not be authorized to prior to this publication.In addition, the date of the publication that provides here may be different with the publication date of reality, may need to be confirmed separately.

To at length introduce the present invention below.Further introducing when of the present invention, at first introducing and be suitable for representational integral biosensor/skin penetrating/liquid acquisition device of using with the present invention.Next introduction topic is stated system and cassette holder device, and subsequent introduction use topic is stated the whole bag of tricks of system and device, and introduces the method for the detection that is used to control the physiologically sample characteristic.At last, topic is stated complete utensil carried out concise and to the point introduction, described complete utensil comprises that being used for enforcement topic states the topic of method and state cassette holder and/or system.

In the introduction below, will in using, analyte concentration determination introduce the present invention; Yet this does not limit the present invention, those skilled in the art will appreciate that it also is useful in the measurement of other physics of biological substance and chemical characteristic such as blood coagulation time, blood cholesterol levels etc. that topic is stated device, system and method.

Representational biology sensor/skin penetrating/liquid acquisition device

The present invention can adopt the various embodiment of biology sensor/skin penetrating/liquid acquisition device (being also referred to as biosensor arrangement here).Biology sensor/skin penetrating/liquid acquisition the device that is suitable for using with the present invention generally has the biosensor components that adopts calibration tape or cushion block form, for example galvanochemistry, colorimetric or luminosity measurement band, and have the skin-piercing element that adopts microneedle or aculea blood aciculiform formula.With reference now to Figure 1A,, 1B, 2A, 2B, 3,4,5A and 5B have wherein shown this representational device.

Figure 1A and 1B have shown this representational biosensor arrangement 2, and it is disclosed in the unsettled U.S. Patent application that the attorney docket of above quoting is No.035, and this application is incorporated herein by reference.Biosensor arrangement 2 comprises the electro-chemical test band structure and forms the microneedle 6 of one with it.Biology sensor is formed by electrochemical cell, and it generally has two spaced apart and electrode of opposite 3 and 5, and here they are called as hearth electrode 3 and top electrode 5 respectively.At least the surface of facing mutually on the electrode 3 and 5 comprises conductive layer 8 and 16 respectively, for example is deposited on the metal on inert substrate 4 and 18 respectively.Spacing between two electrodes is brought by the existence that is positioned at or is clipped in the wall 12 between electrode 3 and 5.Wall 12 preferably has biadhesive so that electrode 3 and 5 is fixed together.Wall 12 preferably is configured to or is cut into can provide reaction zone or zone 9.In reaction zone 9, be provided with redox reaction agent system or composition, its be chosen to particularly can be during sample chemical examination with fluid sample in target component interact.Redox reaction agent system is deposited on the conductive layer of top electrode 5, and when being in the form (shown in Figure 1B) that is fully assembled, redox reaction agent system is in the reaction zone 9.In this structure, hearth electrode 3 is as counter electrode/reference electrode, and top electrode 5 is as the working electrode of electrochemical cell.Yet in other embodiments, according to the contact potential series that is applied on the battery, the role of electrode can reverse, make hearth electrode 3 as working electrode and top electrode 5 as counter electrode/reference electrode.

Microneedle 6 and hearth electrode 3 forms one and therefrom extends out along the plane identical with hearth electrode 3, and ends at sharp-pointed cone point 24 places at far-end, and it helps to thrust in user's the skin.Microneedle 6 also provides the structure that can form the space, and its form is the recessed cavity 20 that is positioned at its end face.This cavity has formed corresponding space in skin histology when microneedle 6 thrusts skin.Tank or aggregation zone are gathered as sample liquids in this space, wherein accumulate in this space before the fashionable liquid that discharges of thorn is being sent in the electrochemical cell.As selection, microneedle 6 also can comprise the opening 22 with cavity 20 fluid communication, to promote the aggregation velocity of physiological fluid in formed aggregation zone.

Biosensor arrangement 2 comprises that also sample liquids transmits or extraction path or path 10, and it extends in the biology sensor from cavity 20.At least a portion of path near-end 10a is in the biology sensor part of device 2, specifically is positioned at reaction zone 9, and the part of the far-end 10b in path 10 is in the microneedle 6.Path 10 is sized to and can applies capillary force to the liquid in the aggregation zone that is formed by cavity 20, and with the physiologically sample extraction or in capillary action is drawn to reaction zone 9.Subchannel 15 laterally extends in a part or the entire reaction district 9 from the proximal part 10a in path 10.Subchannel 15 has promoted the filling of sample liquid in reaction zone 9.

Fig. 2 A and 2B have shown another suitable embodiment of biology sensor/skin penetrating/liquid acquisition device 30, and it also is disclosed in the unsettled U.S. Patent application that attorney docket is No.LIFE-035.Device 30 microneedles 32 that have luminosity/colorimetric bio sensor construction and form one with it.Colorimetric or photometric biosensor generally include these following parts at least: support member or substrate 34, and it is made by inert material such as plastics or metal material; Be used to accept matrix (matrix) zone 36 of sample; Be in the reactant composite (not illustrating as structural member) in the matrix region 36, it generally includes the one or more elements in the analyte oxidation signal generation system; The exhausr port (not shown); And the top layer 38 that has covered matrix 36 at least.In further embodiments, top layer 38 can be to contain the barrier film that is immersed in reactant composite wherein, and matrix region 36 can be contained or do not contain reactant composite.In addition, calibration tape 30 can comprise the double-sided adhesive layer 40 between substrate 34 and barrier film 38, is used for substrate 34 and barrier film 38 are fixed.Double-sided adhesive layer 40 comprises cut-away portions 42, the zone that it is covered corresponding to matrix 36, and formed the zone that is used to deposit the physiological fluid of sampling and is used for each element of signal generation system.

Microneedle 32 and substrate 34 forms one and therefrom extends out along the plane identical with substrate 34, and has the structure that can form the space, and its form is an opening 44, and this opening extends perpendicular to size of microneedle 32 such as width or thickness.The same with the cavity 20 of above-mentioned microneedle 6, when microneedle 32 penetrated in the skin, opening 44 had formed in-house open spaces.This open spaces is gathered tank as sample liquids, wherein is injected in this space before the fashionable liquid that discharges of thorn is being sent in luminosity/colorimetric unit.

Biosensor arrangement 30 accommodates sample liquids and transmits or extract path 46, and it has the far-end 46b that extends and end at distal openings 48 places in the part of microneedle 32.At least a portion of the near-end 46a of passage 46 is in the biology sensor part of device 30, specifically is in the matrix region 36.The size configurations in path 46 becomes can be to applying capillary force by the liquid in the opening 44 formed accumulator region, and physiologically sample is extracted into or is drawn onto in the matrix region 36 through capillary action.Subchannel 50 extends laterally to from the proximal part 46a in path 46 in a part or the whole substrate zone 36, and subchannel has promoted the filling of sample liquid in matrix region 36.

Fig. 3 has shown another the representational biosensor arrangement 60 that is suitable for using with the present invention, and it is disclosed among the unsettled U.S. Patent application No.09/923093, and described application is incorporated herein by reference.Device 60 has the electro-chemical test band structure of the device 2 that is similar among Figure 1A and the 1B, it has first electrode 62 that has relevant inert substrate 64, second electrode 66 that has relevant inert substrate 68, and being positioned between the two wall 70, they have formed the reaction zone 72 with suitable redox reaction agent system jointly.With described to extend a microneedle from its electrode or substrate different as the device of Fig. 1 and 2, device 60 has a plurality of skin-piercing element 74, and they extend from wall 70 and are in basically in the same plane with it.Skin-piercing element 74 can be by making with wall 70 identical or different materials.Each skin-piercing element 74 all has fluid passage 76, its at proximal extension in wall 70 and arrive reaction zone 72.Each fluid passage 76 is opened towards external environment condition along first side 78 of each skin-piercing element and a big segment length of second side 80, and end at skin-piercing element 74 distal tip 82 near.Being sized for of passage 76 can apply capillary force, to gather and to transmit the physiologically sample that is obtained by skin-piercing element 74.Have a liquid path 76 though each skin-piercing element is shown as, yet in each skin-piercing element 74, can use a plurality of this paths.

Fig. 4 has shown another suitable embodiment of the biology sensor/skin penetrating/liquid acquisition device 90 with angled structure.Device 90 comprises two puncture/liquid sample microneedles 92, and each pin includes from distal openings 94 and extends to the reaction zone of near-end biology sensor 98 or the flow path 96 the matrix region 100.Angled structure is generally elongated structure, it is characterized by to have a near sweep of center that is positioned at slim-lined construction.The quantity of skin penetrating structure and the quantity of flow path can change, and general in about scope of 1 to 5, in about scope of 1 to 4, in about scope of 1 to 3, wherein the quantity of puncture component is generally 1 to 2 in many examples more at large usually.The angle of sweep is generally in about 135 ° to 150 ° scope, more at large in about 140 ° to 145 ° scope.Most advanced length from sweep to elongated angled structure is generally in about 2.3 to 3.2 microns scope, more at large in about 2.6 to 3.0 microns scope.

Flow path of the liquid 96 has capillary dimensions, its can make the physiological fluid that obtained from distal openings 94 along flow path length and capillary flow to biology sensor 98.Because flow path is the path with capillary dimensions, thus flow path along the diameter at any point place of its length usually in about 80 to 150 microns scope.Flow path can be tubulose or have some other structure, for example cross sectional shape is the structure of square, rectangle, ellipse, star etc., wherein the structure of flow path is not critical, as long as it can provide needed capillary flow.

Biology sensor 98 generally is made of the sensor cavities that includes conversion equipment, and described conversion equipment can be in response to the analyte in the physiological fluid in the chamber, typically be the existence of analyte concentration and produce signal.The chamber that is positioned at the proximal end of device 90 generally has the volume in the scope of about 100 to 300 microlitres.Conversion equipment can be any conversion equipment easily that can produce signal in response to the analyte in the liquid in the chamber exists.Can produce the signal of having represented that analyte exists although say conversion equipment in a broad sense, in many preferred embodiments, conversion equipment be can produce with physiological fluid in the device of amount of analyte proportional signal.

Can be present in one type the conversion equipment of being concerned about stated in the sensor of topic is the luminosity conversion equipment.The luminosity conversion equipment of being concerned about generally comprises one or more reactants of signal generation system, described signal generation system can produce with chamber in amount of analyte proportional can detected product.To carrying out photometric detection by detected product, to carry out the detection that analyte exists, it is generally the measurement to the analyte concentration in the liquid in the chamber subsequently.The interesting luminosity conversion equipment that adopts in this biosensor arrangement includes but not limited to that these patents are incorporated herein by reference at the device described in U.S. Patent No. 4935346, No.5049487, No.5509394, No.5179005, No.5304468, No.5426032, No.5563042, No.5843692 and the No.5968760.

It is another kind of that can be present in the conversion equipment of being concerned about that topic states in the sensor be the electro-chemical conversion device.The electro-chemical conversion device of being concerned about generally comprises electrochemical cell, and it comprises one or more reactants of two electrodes and signal generation system, and wherein these parts collaborative works are with the proportional electric current of amount of analyte in generation and the chamber.The electric current that is produced can be used for the existence of check and analysis thing, is generally the concentration of measuring the analyte in the liquid that is present in the chamber.The electro-chemical conversion device of being concerned about that can be used in the biosensor arrangement includes but not limited to that these open source literatures are incorporated herein by reference at the device described in U.S. Patent No. 5834224, No.5942102 and No.5972199 and U.S. Patent application No.09/333793, No.09/497269 and the No.09/497304.

Fig. 5 A and 5B have shown another representative embodiment that is suitable for biology sensor/skin penetrating/liquid acquisition device 110 of using with the present invention, this device is disclosed in the unsettled U.S. Patent application that the above-mentioned attorney docket of quoting is No.058, and this application is incorporated herein by reference.Device 110 comprises plane framework 112, be installed on the framework 112 and by its blade section of carrying 114 and Sensor section 116.Blade section 114 comprises the intermediate wedge part or lifts part 118, the blade that is substantially transverse to plane framework 120 and extends has been installed on it or has been thrust part 120.Part 118 is used to make blade or thrusts part 120 lift with respect to the surface or the face 122 towards skin of framework 112.Lift part 118 and have angled front surface or chamfered portion 124, it allows device 110 to carry out level and smooth translation motion with respect to user's skin.Also be provided with land regions 126, blade 120 just is mounted thereon, the narrow structures of land regions 126 be used to reduce and user's skin between friction force, improved the ability that is positioned at this structural tissue that presses down simultaneously.Blade 120 has triangular shaped, and it has the bigger pedestal and the lateral parts of approximate vertical, yet blade 120 can have the enough firm Any shape to avoid fractureing of its geometric configuration.Sensor section 116 is spaced apart with blade section 114, evenly engages basically with the cut-out region of user's skin to allow Sensor section 116.Sensor section 116 provide be used to receive the physiological fluid that obtained, be the sensor cushion block or the zone 128 of interstitial fluid or blood.Sensor cushion block 128 can have aforesaid electrochemical structure or luminosity structure.

Although shown and introduced the ad hoc structure that is suitable for biology sensor/skin penetrating/liquid acquisition device of using with system of the present invention, yet should be appreciated that the biology sensor of any kind such as the sensor of galvanochemistry, luminosity or colorimetric all can use with one or more suitable skin puncture components or microneedle.In addition, although shown and introduced the given shape of skin-piercing element and microneedle, yet can adopt the skin-piercing element of any suitable shape to use, as long as this shape allows and can thrust skin with minimum pain concerning patient with biosensor arrangement.For example, skin-piercing element can have the structure smooth basically or plane, or is essentially cylindrical, wedge shape, triangle such as the leg-of-mutton structure of general flat, and blade shape perhaps has any other suitable shape.At least that part of cross sectional shape that thrusts in the skin of skin-piercing element or skin-piercing element can be any suitable shape, includes but not limited to roughly rectangle, rectangle, square, ellipse, circle, rhombus, triangle, star etc.In addition, skin-piercing element can be taper, perhaps otherwise on its a terminal point or summit of forming.It is the form at oblique angle that this structure can be taked at the tip, or pyramid or leg-of-mutton shape etc.The size of skin-piercing element can change according to various factors, the type of physiologically sample for example to be obtained, the required skin layer thickness that thrusts the degree of depth and given patient to be tested.In general, skin-piercing element is configured to provide the function of skin penetrating and Liquid extracting, so it should be designed to enough firmly be inserted into skin neutralization and extract out from skin to bear.

In each embodiment, when cassette holder device of the present invention that biology sensor/skin penetrating/liquid acquisition device construction Cheng Dangyu hereinafter will introduce in detail and system used together, it can provide with physiological fluid and obtain repeatably engaging between position and the target skin layer.

System of the present invention

With reference to figure 6A, 6B, 6C and 6D have shown physiologically sample collection of the present invention and measuring system 200 with compactness, portable planform among the figure.This structure comprises the shell 202 that has by the human engineering design of hinged top 204 of hinge means 208 and bottom 206, and hinge means 208 allows can make when manually actuating button 226 grades that can depress top 204 and bottom 206 to open and close.Fig. 6 D has shown this shell 202 that is in open mode, and Fig. 6 A, 6B and 6C have shown the shell 202 that is in closed condition.Cover top portion 204 and outer casing bottom 206 have formed inner volume together, and cassette holder device 210 of the present invention is operationally packed into and wherein and after use taken out.As following introduce in more detail with reference to figure 7A and 7B, cassette holder 210 holds or provides one or more, is generally a plurality of biology sensors/liquid acquisition device 220.

When in the inner volume of the shell of correctly packing into, the bottom surface of cassette holder device 210 is placed near the inboard of diapire 212 of outer casing bottom 206.Diapire 212 preferably has the outer surface structure, and this structure is smooth, and can form concordant with the selected zone of user's skin as required.In diapire 212, be provided with opening 214; shown in Fig. 6 C; its size and position make a biology sensor/liquid acquisition device 220 to aim at and come out by opening 214, and remaining biology sensor/liquid acquisition device 220 is hidden and protects in diapire 210.Opening 214 and contact device (not shown) such as electrical lead or similar device link to each other, be used for when device 220 is in opening 214 device 220 be contained in shell 202 in measuring instrument or the measurement mechanism (not shown) between carry out communicating by letter of electric signal.This electric signal comprises from the input signal of measuring instrument auto levelizer 220, it is used to start the chemical reaction between the reactant in sample liquid and the device 220, from user's skin, obtain and the chemical characteristic of the liquid of sampling so that measure, for example the concentration of analyte (as glucose) by installing 220.

This measurement mechanism has and installs compatible necessary structure and the parts of biology sensor type, for example galvanochemistry, luminosity or colorimetric sensor that adopted on 220.In based on electrochemical measuring system, the electrochemical measurement that is carried out can change according to chemical examination type of measuring and the measuring instrument that is adopted, and is that electrical measurement, current measurement or potential measurement change according to chemical examination for example.In general, electrochemical measurement will be measured electric charge (electrical measurement), electric current (current measurement) or current potential (potential measurement), and measure after sample is introduced in the reaction zone one period preset time usually.The method that is used for carrying out above-mentioned electrochemical measurement has further introduction at U.S. Patent No. 4224125, No.4545382 and No.5266179 and international monopoly publication WO 97/18645 and WO 99/49307, and these open source literatures are incorporated herein by reference.In luminosity/colorimetric chemical examination, adopt the optical type measuring instrument to chemically examine.This chemical examination and method and being used to carried out the instrument of these chemical examinations and method in U.S. Patent No. 4734360, No.4900666, No.4935346, No.5059394, No.5304468, No.5306623, No.5418142, No.5426032, No.5515170, No.5526120, No.5563042, No.5620863, No.5753429, No.5773452, No.5780304, No.5789255, No.5843691, No.5846486, further introduction is arranged among No.5968836 and the No.5972294; These patents are incorporated herein by reference.

System 200 also comprises and is used for operationally making the device of cassette holder 210 in shell 202 motions, thereby can make cassette holder 210 motions so that sequentially locate each biology sensor/liquid acquisition device 220 at opening 214 places or with respect to opening 214.The motion of this cassette holder comprise with respect to opening 214 along a direction such as clockwise direction promote cassette holder 210 and in opposite direction as counter clockwise direction make cassette holder 210 counter motions so that device 220 is aimed at opening 214 and device 220 exposed from opening 214 or stash.This cassette holder telecontrol equipment can be an electric motor driven system etc., or drives by ring or the leverage cause user artificially that is located at shell 202 outsides.In electric motor driven system, cassette holder 210 can be provided with driving wheel 232, makes that when cassette holder device 210 is operationally packed into and is positioned at shell 202, driving wheel 232 engages with driving shaft 234, so that the edge forward or opposite direction rotation cassette holder 210.Driving shaft 234 drives by also being positioned at cavity volume 230 internal driving electric machines.

System 200 also comprises the biology sensor telecontrol equipment (not shown) that links to each other at opening 214 places with cassette holder 210, so that apply acting force on 220 to being positioned at respectively installing of opening 214 places.This biology sensor telecontrol equipment can make device 220 all move downward cassette holder bottom surface thereon, position from all devices 220, and by opening 214 device 220 is operationally contacted with selected skin area.This exercisable contact comprises by being located at the skin-piercing element of respectively installing on 220 punctures, cuts or thrust skin surface.Can adopt any device easily that can apply this downward acting force at device 220, wherein representational device comprises spring assembly or the similar mechanical hook-up that will be explained in greater detail below, or the like.

System 200 also comprises controller, it has the microprocessor operating that is used for control survey device, data processing equipment, automatic cassette holder telecontrol equipment, and the display 218 that is used to show measurement data and other related data, for example notified the user with out-of-date at all devices 220.Microprocessor also can link to each other with memory storage, so that short-term or storage of measurement data chronically.System 200 also can comprise communication module, it is used for for example also for example coming to carry out two-way communication with telechiric device or other device by infrared (IR) transmission or radio frequency (RF) transmission by wireless data communication device such as telemetering device, so that chemically examine communicating by letter of scheme program and information, and be used for carrying out behind instant or the order retrieval of measurement data, or the like.System 200 also is provided with user's operating key 224 on shell 202, allow user input data or parameter or selection to be shown in data or parameter on the menu of display, perhaps start the motion and the chemical examination scheme of cassette holder, wherein representational data-signal is sent to system controller.System 200 is may command vision or audio alarm device also, and it can remind the user when cassette holder and analysis measurement are in outside the safe range etc. should chemically examining, need to change.Also be provided with power supply and battery so that provide electric energy for the motor of cassette holder, microprocessor and all parts by microprocessor control.

The system unit of just having introduced above can be contained in the sealed volume 230 of protectiveness, and wherein data necessary or signal wire for example can arrive outer casing bottom 206 through hinge 208 from the cavity volume the cover top portion 204 230.Perhaps, this data or signal wire can be located in the cover top portion 204, make that they can contact with corresponding data or the signal wire in the outer casing bottom 206 when shell is in closed condition.

With reference now to Fig. 7 A,, shown among the figure to be suitable for and Fig. 1 at least the diagram of an embodiment of the cassette holder device 300 of the present invention that the biology sensor/skin penetrating shown in 2 and 3/liquid acquisition device uses together.Cassette holder device 300 has cassette holder main body or framework 302, and establish thereon a plurality of integrated biology sensor/skin penetrating/liquid acquisition device 304 (being also referred to as biosensor arrangement here), device 304 preferably sequentially is provided with and separates equably each other.Cassette holder of the present invention can load the integral biosensor device 304 of any right quantity, and wherein the quantity of cassette holder is generally in about scope of 6 to 10.

In the ring-type or disk-like structure of Fig. 7 A, cassette holder main body 302 by concentric frame loops, be that outside framework ring 302a and inner frame ring 302b form.Ring 302a and 302b relatively are fixed together by a plurality of torsion bars 306 that extend between ring 302a and 302b.Framework 304 is made by the material of any rigidity, for example injection molded such as makrolon material, and torsion bar 306 preferably makes to be that the material of deflection or twist and warping is made around its longitudinal axis by its performance and/or size, for example thickness in about 50 to 75 microns scope, the stainless steel of width in about 0.5 to 1 millimeter scope.Each integral biosensor device 304 operationally links to each other with torsion bar 306, is preferably between device 304 and the torsion bar 306 to concerning one to one.Each torsion bar 306 allows corresponding continuous device at least in part around being rotated with respect to framework 304 by the formed longitudinal axis of torsion bar.Therefore, this turning axle is perpendicular to the path of cassette holder 300 rotations or operation.The diameter of cassette holder 300 generally in about 3 to 4 centimetres scope, wherein in the center of dish and the distance between the biosensor arrangement usually in about 7 to 9 millimeters scope.

As mentioned above, cassette holder device 300 also can comprise driving wheel 308, and it can link to each other with the driving shaft in being contained in the system 200 that cassette holder device 300 is housed.Perhaps, driving wheel 308 also can be contained in the system shell with being separated, and is configured to accept cassette holder framework 302 and engages with it.Driving wheel 308 comprises wheel hub 310 and a plurality of frame bars 312 that are fixed on the inner frame ring 302b.The rotation of driving wheel 308 makes cassette holder main body 302 produce the rotation translation, and therefore makes device 304 produce the rotation translation around wheel hub 310.

Fig. 7 B has shown and operationally has been positioned at the cut-away portions of cassette holder device 300 that the topic with opening 316 is stated the outer casing bottom 314 of system.The width of opening 316 is enough to make biosensor arrangement 304 to pass through, and it is generally in about 3 to 8 millimeters scope, usually in about 4 to 6 millimeters scope.The parts 320a and the 320b of biology sensor telecontrol equipment operationally are fixed in the system shell, and lay respectively at the front side 318a of opening 316 and opposite side 318b near.Parts 320a has the structure of wedge shape, and parts 320b has spring-loading clamping structure.As among Fig. 8 A-F best shown in, biology sensor moving component 320a has top plane 322 and downward angled front 324, and biology sensor moving component 320b has that elasticity loads or bias voltage leans against top clamping element 326 on the clamping element 328 of bottom.Parts 320a be positioned on the outer casing bottom 314 and cassette holder device 300 under, and parts 320b is located such that the Plane of rotation of cassette holder device 300 and biosensor arrangement 304 passes through between clamping

element

326 and 328.

With reference now to Fig. 8 A-F, is presented in the motion that biology sensor 304a is carried out in the process of chemically examining application.Cassette holder device 300 preferably is arranged so that when not moving does not have biosensor arrangement 304 in the opening 316, thereby has prevented to the pollution of biosensor arrangement and to user's unexpected injury.In addition, each installs 304 by being applied to the tension force on the device 304 and being remained on the position on plane basically with respect to outer casing bottom 314 by torsion bar 306.Along the direction of arrow 330, be that counter clockwise direction among Fig. 7 B promotes or rotate the cassette holder device biosensor arrangement 304a will be advanced or rotation along equidirectional, thereby near parts 320b.When device 304a was pushed into, it (saw Fig. 8 A) with regard to wedge between top clamping element 326 and bottom clamping element 328.When clamping element is biased in a time-out mutually, biosensor arrangement 304a when being between clamping element 326 and 328 and parts 320b form rubbing contact.When biosensor arrangement 304a along the direction of arrow 332 by enough promotions so that its back of the body end or near-end 334 when being between clamping element 326 and 328, parts 320b applies slight upwards acting force or pressure on biosensor arrangement 304a, thereby make device 304a around torsion bar 306 rotations, and the front end of device 304a or most advanced and sophisticated 336 deflect down (seeing Fig. 8 B) towards opening 316.When device 304a when the direction of arrow 338 is further pushed ahead, the front end 336 of deflection can contact with the angled front 324 of wedge shape part 320a (seeing Fig. 8 C), thus along downwards and direction forward acted on further or deflection.At this moment, this deflection and motion forward are enough to make the skin-piercing element 340 of device 304a to be thrust in user's the targeted skin surface (not shown).Thrust in the process this, physiological fluid such as interstitial fluid or blood are acquired and are drawn in the biology sensor part of device 304a, so that detected by the measurement component of system.Through being used to obtain and gather the sufficiently long time of physiological fluid sample after, cassette holder device 300, is actuated up to device 304a and moving component 320a and 320b disengagement and by torsion bar 306 and is got back to its initial plane position with respect to cassette holder ring 302a and 302b (seeing Fig. 8 E) as clockwise direction (seeing Fig. 8 D) motion along opposite direction 342.At last, cassette holder 300 is once more along forwards advancing to 346, and up to the device 304a that crosses (seeing Fig. 8 F) till the opening 316 by Fig. 7 B fully, cassette holder 300 is locked in place at this moment, thus the injury that prevents to move unexpectedly and may cause the user.When the user starts the chemical examination scheme, come this process of repetition with each device 304.When all devices 304 all by with out-of-date, when promptly being used to chemically examine scheme, can from system shell, taking out with the cassette holder of mistake and with it and correctly abandon.In the system of then cassette holder that substitutes being packed into.

With reference now to Fig. 9 A-9G,, shown another embodiment that is particularly suitable for the biology sensor telecontrol equipment 400 that uses with biology sensor/skin penetrating shown in Figure 4/liquid acquisition device among the figure.Biology sensor telecontrol equipment 400 comprises isolated parts 402a and the 402b that is arranged in the shell of inscribing the system that states.Parts 402a and 402b are spaced apart, thereby on the opening 401 in the outer shell bottom wall, as mentioned above, and provide surface and edge to pass through opening 401 with guiding biosensor arrangement 404, so that operationally contact with user's targeted skin surface zone.The surperficial gradient and the edge angle of this surface and edge and biosensor arrangement 404 are complementary.More particularly, parts 402a has angled surperficial 410, and the back side 412 of itself and angled biosensor arrangement 404 is complementary.Angled surperficial 410 bottom surfaces 414 general and parts 402a form angle α, and it is in about 40 ° to 55 ° scope, more at large in about 45 ° to 50 ° scope.In addition, parts 402b has the end face 406 that engages with the bottom surface 408 of angled biosensor arrangement 404, and has the angled back side 416 that the front surface 418 with angled biosensor arrangement 404 is complementary.416 bottom surfaces 420 general and parts 402b, the angled back side form angle β, and it is in about 30 ° to 50 ° scope, more at large in about 25 ° to 35 ° scope.

With reference now to Fig. 9 A-9G, is presented in the motion of biology sensor 404 in the process of testing.The same with Fig. 7 A with 73 described embodiment, biosensor arrangement 404 can be rotationally connected by the torsion bar (not shown) or by the pivot with wheel hub/spoke (seeing Figure 10 A-10C) and be operatively coupled on the cassette holder (not shown), make biosensor arrangement 404 can remain on the initial bias voltage position, it is concordant with the end face 406 of parts 402b wherein to install 404 bottom surface 408.In Fig. 9 A, angled biology sensor 404 moves along the first direction according to arrow 422, crosses the end face 406 of parts 402b.Fig. 9 B shown when angled biology sensor 404 when the direction of arrow 424 is moved and cross gap between parts 402a and the 402b, it drops into downwards in two openings between the parts, and moves along the inclined surface 410 of parts 402a.At this moment, the direct of travel of angled biology sensor 404 is opposite, shown in Fig. 9 C, this direction be shown in the arrow 426 forwards to.Because the downward acting force that cassette holder applied, angled biology sensor 404 continues to move down along inclined surface 410, makes that the bottom surface 408 of angled biology sensor 404 is concordant with the targeted skin surface that comes out by opening 401.Angled sensor 10 makes the front surface 418 of angled biology sensor 404 contact with the surface 416 of the reversal dip of parts 402b along move forward (the seeing Fig. 9 D) of arrow 428 directions.This contact impels biology sensor 404 further to move downward and enter into targeted skin surface, make the skin penetrating structure 430 of biology sensor 404 penetrate into the selected skin layer of targeted skin surface, for example corium, epidermis, hypodermis etc., thereby obtain physiological fluid such as interstitial fluid or the blood be concerned about, but the capillary flow path of its filled biomass sensor 404.

Sampling and liquid filling after the capillary flow path of biology sensor 404, biology sensor 404 moves along the first direction of the arrow shown in Fig. 9 E 432 once more.Biology sensor 404 continues to move and makes biology sensor 404 take out the position from skin surface/sampling along opposite first direction, and make biology sensor 404 upwards leave opening between parts 402a and the 402b, shown in Fig. 9 F and shown in the arrow 434.In case angled sensor leaves opening, shown in Fig. 9 G, just can chemically examine (certainly, also can chemically examine liquid when needed, this depends on the preferred sampling/measurement scheme that is adopted) to the liquid in the biology sensor chamber when sensor still is in original position.When the user starts the chemical examination scheme, repeat this process with each biology sensor 404.When all devices 404 all are used, when promptly all being used to carry out the chemical examination scheme, can taking out from system shell with the cassette holder of crossing and with it and correctly abandon.In the system of then cassette holder that substitutes being packed into.

Below will be according to further showing cassette holder telecontrol equipment to the representativeness shown in 10C rotation cassette holder device with reference to figure 4 to 9 embodiment that introduced as Figure 10 A.In Figure 10 A, rotation or plate-like cassette holder 440 comprise eight angled biology sensors 442, and are positioned at the top of the bottom surface 444 of the shell (not shown) that wherein has opening 446.In use, cassette holder 440 rotates along first clockwise direction 448 shown in Figure 10 A, thereby operationally locatees biology sensor 442 with respect to the biology sensor telecontrol equipment according to Fig. 9 A and 9B.Then that the sense of rotation of cassette holder is reverse, become the counter clockwise direction 450 shown in Figure 10 B, it enters in the opening 446 in the bottom surface 444 biology sensor 442a, wherein penetrates in the targeted skin surface zone, obtain physiological fluid, and send it in the chamber of biology sensor 442a.Then, the sense of rotation of cassette holder 440 is reverse once more, becomes the clockwise direction 452 shown in Figure 10 C, and it is extracted biology sensor 442a out from skin, then the analyte in the liquid that is obtained is measured.

By the minor modifications that it will be appreciated by those skilled in the art that, with reference to biosensor structure that above-mentioned Fig. 5 introduced can with Fig. 7 and 8 or the cassette holder embodiment of Fig. 9 and 10 and cassette holder separately thereof and biology sensor telecontrol equipment use similarly.Like this, topic is stated the cassette holder and the corresponding construction of system and can many different modes be constructed, as long as the cassette holder device can continue to use in carry out the chemical examination scheme forwards to handling with reverse direction, and biology sensor can operationally be handled by the biology sensor telecontrol equipment of system, makes that being located at biology sensor on the cassette holder can thrust skin surface and obtain wherein physiological fluid.

This device can adopt multiple different structure with system.In certain embodiments, device is single unitary device, and wherein measurement mechanism, treating apparatus, display device etc. all are located on the same structure.In further embodiments, one or more parts can separate with other parts.For example, measurement mechanism can separate with display device, wherein adopts telemetry communication or analyzes data transmission device such as radio frequency or RF device are provided at data communication between two or more separate parts of device.

A representational topic is stated embodiment " watchband " embodiment shown in Figure 11 A of system, wherein installs 500 and is configured to and can be worn on limb part 502 as on the forearm with mode like the watch kind.In this embodiment, all parts of device can be located in the integral unit, wherein this element by adjustable with 504 or other holding device and keeping in touch with user's skin.

State part that system can see with user's difficult quilt, for example covered by clothes usually or useless (waste) part of otherwise being difficult for being seen or other parts when contacting in hope topic, can adopt the two-piece type system shown in Figure 11 B.In such an embodiment, cassette holder device and measurement mechanism, be that biology sensor and measuring instrument are located at parts as in " watchband " parts 506, and show and control device is located at second parts of system as in the remote control unit 508 of handing.The intercommunication mutually by data communication equipment (DCE) of these two parts, wherein data communication equipment (DCE) is generally wireless data communication device, for example rf telemetry device.

In some other embodiment of the present invention, topic is stated system does not need the band or the band that are used to connect, but can be connected on the suitable skin area by biocompatible bonding agent.

Method of the present invention

Topic is stated system and device and be can be used for measuring the characteristic of physiological fluid, more typically is the method for the analyte concentration in the measurement physiological fluid.When enforcement topic is stated method, be provided with respect to user's targeted skin surface zone and the location has integral biosensor and skin-piercing element, as the described device of above-mentioned various embodiment.The integral biosensor device can or move to second place expansion or contact skin from initial or retrieving position motion, thrusts in the target surface in this position and obtains physiological fluid, and send it to the biology sensor part of device.Can make the translation or the reversing of motion of device, from skin, take out and regain installing.

When stating the cassette holder device with above-mentioned topic and use, provide a plurality of this integrated biosensor arrangement that operationally engages with the cassette holder device.The setting of cassette holder device also is positioned to and the regional coplane of user's targeted skin surface.Adopt telecontrol equipment that cassette holder is moved or translation along first direction, it can make biosensor arrangement from initial or retrieving position motion or move to second place expansion or contact skin, thrust in the target surface in this position and obtain physiological fluid, and send it to the biology sensor part of device.Actuate telecontrol equipment subsequently, the cassette holder device is moved or translation along direction second or reverse, retrieving position is got back in its second place motion or translation that from then on biology sensor is launched.Biosensor arrangement from retrieving position to contact this motion of skin site and opposite motion can finish further to the angled or inflection point that is used to contact and thrust skin from the location deflection of general plane by making biosensor arrangement.

When stating system with above-mentioned topic and use, the cassette holder device is located at or is encased in to have in the shell mechanism in hole in the wall of skin.Outside surface towards the wall of skin preferably is positioned as concordant with user's targeted skin surface zone.The cassette holder device is positioned at shell mechanism, make its with towards the surface co-planar of skin, and the translation of a plurality of biosensor arrangements is in directly in the path on opening.When the motion of carrying out aforesaid cassette holder or translation, the motion of particular organisms sensor device or deflection comprise make at least skin-piercing element by this opening with contact and thrust skin surface.

Topic is stated method and is also comprised aforesaid measuring instrument or measurement mechanism, and it operationally contacts with biosensor arrangement, so that the selected characteristics that is sent to the sampling physiological fluid in the biosensor arrangement after obtaining physiological fluid is measured.After having filled the reaction zone or matrix region of biosensor arrangement with the sampling physiological fluid, the measuring instrument parts of stating system by topic are applied to signal on the biology sensor, and the chemical characteristic that measurement is concerned about is analyte concentration for example, show resulting measurement data by the display that is located on the system shell, and with this data storage in memory storage for retrieving behind instant or the order.

Topic is stated methods, devices and systems and be can be used in the various application scenario, wherein needs to measure the analyte in the physiological fluid and/or analyte concentration measured.Topic is stated system, apparatus and method and especially is used in the monitoring application of carrying out analyte concentration in one given period, described in for example unsettled U.S. Patent application No.09/865826, this application is incorporated herein by reference, wherein can automatically carry out the sampling/measurement of physiological fluid, and carry out constantly according to preset program.

In these monitorings were used, the present invention can be used for: (a) monitor the concentration analyte relevant with the patient's condition continuously, for example hypoglycemia in the blood sugar disorders or hyperglycemia are as diabetes; (b) monitor the analyte of concentration and the non-disease physiological status be concerned about continuously, for example use of alcoholism, illegal drug; (c) monitor the concentration of the healing potion of drug therapy in using continuously, or the like.

When analyte was glucose, the present invention can be used in the different application of the treatment of the multiple patient's condition relevant with glucose and control, for example diabetes and related conditions etc.In these embodiments, topic is stated the glucose monitoring that method and apparatus can be used for providing " continuously ", and it is meant and can arrives according to the glucose level that preset program discontinuously and automatically measures in the patient body.Also can the employing topic state the generation that method detected and predicted the hypoglycemia and the hyperglycaemia patient's condition.In these were used, figure and contrast figure or reference pattern by relatively being stored in the measurement result in the system memory device can adopt the figure of the analyte concentration measurement of continuous monitoring to determine whether patient suffers from hyperglycaemia or hypoglycemia.In addition, the operator can observe measurement pattern and itself and suitable contrast or reference pattern are compared, with the generation of the prediction hypoglycemia and the hyperglycaemia patient's condition.It can be a part that is designed to prevent the more fully therapeutic scheme that the hypoglycemia and the hyperglycaemia patient's condition take place that topic is stated method, this be for example by with inscribe state that method and apparatus is predicted the generation of this class patient's condition and preventing the mode of the patient's condition of being predicted disturb the metabolism of blood sugar to realize.

The present invention can be used for wishing to carry out the various dissimilar use body of analyte monitoring.The use body of being concerned about includes but not limited to mammal.The mammal of being concerned about comprises important domestic animal pack animal, ox, sheep etc., pet such as dog, cat etc., and human.In many examples, to state the mammal of method be human for enforcement thereon topic.

Complete utensil

The present invention also provides and has been used for the complete utensil that the enforcement topic is stated method.In one embodiment, complete utensil comprises that being used for enforcement inscribes the system that states invention.System can be an integrating device, and perhaps for example remote control and display unit and measurement component are formed by two or more parts that separate.Complete utensil can comprise as described above can state the disposable cassette holder device that system uses, perhaps two or more disposable cassette holder devices with topic.At last, complete utensil generally includes and is used for use topic and states system and be used for the cassette holder operation instruction that topic states system and therefrom take out of packing into.These operation instructions can be located at above container in one or more packings, label embolus, the complete utensil etc.

Though for understanding clearly purpose and foregoing invention has been carried out detailed introduction to a certain degree by accompanying drawing and example, yet for the ordinary skill in the art clearly, according to instruction of the present invention, under the prerequisite of the spirit or scope that do not break away from claims, can carry out certain change and modification to content of the present invention.

Claims

1. system comprises:

Multiple arrangement, wherein each described device comprises:

(i) at least one skin-piercing element, it is configured to obtain the physiological fluid under the skin surface;

(ii) be used to measure the biology sensor of the characteristic of the physiological fluid that is obtained, wherein said skin-piercing element and described biology sensor form one;

(iii) physiological fluid transfer path, it extends to described biology sensor from described at least one skin-piercing element; With

Be used to make the mechanism of each described multiple arrangement motion, the mode of described motion provides by described at least one skin-piercing element and penetrates in the skin surface with the angle that is inclination with respect to skin surface.

2. system according to claim 1 is characterized in that each described device comprises the structure on plane, and wherein said at least one skin-piercing element is therefrom extended.

3. system according to claim 2 is characterized in that, described at least one skin-piercing element is extended in the plane identical with described planar structure basically.

4. system according to claim 3 is characterized in that described plane device has formed the biology sensor with calibration tape structure, and described at least one skin-piercing element is extended from described calibration tape.

5. system according to claim 2 is characterized in that, described at least one skin-piercing element is extended along the direction that extends substantially transversely to described plane device.

6. system according to claim 1 is characterized in that, described system also comprises:

Shell mechanism, it has towards the part of skin and is positioned at the opening of described part towards skin;

Be contained in the described shell mechanism and comprise the cassette holder of described multiple arrangement, wherein said mechanism is used to make described cassette holder to move in described shell mechanism, thereby each described multiple arrangement is located with respect to described opening.

7. system according to claim 6 is characterized in that, the described mechanism that is used to described cassette holder is moved makes each described device travel forward with respect to described opening, and moves along opposite direction subsequently.

8. system according to claim 6 is characterized in that, described system also comprises the device of the time of the motion that is used to control described cassette holder and described motion.

9. system according to claim 6 is characterized in that, described shell mechanism is configured to can be worn on the limbs position.

10. system according to claim 6 is characterized in that, described shell mechanism is configured to and can wears round waist.